IONIS PHARMACEUTICALS INC — Director's Dealing 2011

Dec 20, 2011

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2011-12-16

Reporting Person: BENNETT C FRANK (Senior Vice President)

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2011-12-16	Common Stock	M	1500	$5.80	Acquired	1805	Direct
2011-12-16	Common Stock	S	1500	$6.79	Disposed	305	Direct
2011-12-19	Common Stock	M	160	$5.80	Acquired	465	Direct
2011-12-19	Common Stock	S	160	$6.90	Disposed	305	Direct
2011-12-19	Common Stock	M	1340	$5.80	Acquired	1645	Direct
2011-12-19	Common Stock	S	1340	$6.82	Disposed	305	Direct
2011-12-20	Common Stock	M	2000	$5.80	Acquired	2305	Direct
2011-12-20	Common Stock	S	2000	$6.82	Disposed	305	Direct
2011-12-20	Common Stock	M	500	$5.80	Acquired	805	Direct
2011-12-20	Common Stock	S	500	$6.92	Disposed	305	Direct

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2011-12-16	Employee Stock Option (right to buy)	$5.80	M	1500	Disposed	2012-01-02	Common Stock (1500)	Direct
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	1500	Disposed	2012-01-02	Common Stock (1500)	Direct
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	2500	Disposed	2012-01-02	Common Stock (2500)	Direct

Footnotes

F1: Acquired as a result of exercising a stock option that was scheduled to expire on 1/2/12. The purchase and sale reported on this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the reporting person on 6/23/11.